Bristol Myers Squibb and Acceleron Pharma Inc. announced that the European Commission (EC) has approved Reblozyl (luspatercept) for the treatment of: Adult patients with transfusion-dependent anemia due to very low-, low- and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts, who had an unsatisfactory response or are ineligible for erythropoietin-based therapy; Adult patients with transfusion-dependent anemia associated with beta thalassemia.
"Dependence on blood transfusions caused by anemia in hematologic malignancies like MDS can often mean frequent and lengthy hospital visits, which can pose additional health risks and affect patients’ quality of life,” said Uwe Platzbecker, M.D., lead investigator of the MEDALIST study, Head of Clinic and Policlinic for Hematology and Cell Therapy, Leipzig University Hospital. “Today’s approval of Reblozyl provides healthcare professionals with a new therapy that has been shown to significantly reduce the number of red blood cell transfusions needed by MDS patients and, in some cases, helped them to achieve transfusion independence.”
“While beta thalassemia remains an orphan disease, the lifelong blood transfusions often needed by patients can have a significant impact on the limited blood supply in their communities, and there are few treatment alternatives,” said Maria Domenica Cappellini, M.D., lead investigator of the BELIEVE study, Professor of Medicine, University of Milan, Fondazione IRCCS Ca Granda. “The European Commission’s approval of Reblozyl provides eligible adult patients with beta thalassemia a new, much needed treatment option for their anemia, and with it, the possibility of becoming less dependent on red blood cell transfusions.”
Reblozyl is the first and only erythroid maturation agent approved in the European Union, representing a new class of therapy for eligible patients. This approval is based on data from the pivotal phase 3 MEDALIST and BELIEVE studies, evaluating the ability of Reblozyl to effectively address anemia associated with MDS and beta thalassemia, respectively.
“Across the EU, 25 million blood transfusions occur every year, some of which are needed by patients with anemia due to hematologic diseases like MDS and beta thalassemia,” said Diane McDowell, M.D., vice president, Hematology Global Medical Affairs, Bristol Myers Squibb. “Reblozyl has the potential to address the ineffective erythropoiesis associated with MDS and beta thalassemia, decrease patients’ dependence on red blood cell transfusions and impact the underlying consequences of the high burden of anemia for these patients. Alongside our partners at Acceleron, we recognize the continuing need in disease-related anemias and are committed to working collaboratively with European health authorities to make Reblozyl available to these patients as quickly as possible.”
MEDALIST is a phase 3, randomized, double-blind, placebo-controlled, multi-center study evaluating the safety and efficacy of Reblozyl plus best supportive care (BSC) versus placebo plus BSC in adults with IPSS-R-defined very low-, low- or intermediate-risk non-del(5q) MDS. All patients were RBC transfusion-dependent and were either refractory or intolerant to prior erythropoiesis stimulating agent (ESA) therapy, or were ESA naïve and unlikely to respond due to endogenous serum erythropoietin levels of = 200 U/L, and had no prior treatment with disease modifying agents.
The trial showed a statistically significant improvement in RBC transfusion burden with Reblozyl, the study’s primary endpoint, with 37.9% of patients treated with Reblozyl achieving independence from RBC transfusions for at least eight weeks during the first 24 weeks of the trial compared to 13.2% of patients on placebo. The trial also met the secondary endpoint of transfusion independence for at least 12 weeks within the first 24 and 48 weeks of the study, which was achieved in a significantly greater proportion of patients receiving Reblozyl versus placebo.
The majority of treatment-emergent adverse events (TEAEs) were Grade 1-2. Grade 3 or 4 TEAEs were reported in 42.5% of patients who received Reblozyl and 44.7% of patients who received placebo. Discontinuation due to an adverse reaction (Grades 1-4) occurred in 4.5% of patients who received Reblozyl. The most common (>10%) all-grade adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis and urinary tract infection.
Results of the MEDALIST trial were first presented during the Plenary Session of the American Society of Hematology (ASH) Annual Meeting in December 2018 (ASH Abstract #001) and were selected for the Best of ASH. The New England Journal of Medicine published the MEDALIST trial results in January 2020.
MDS are a group of hematologic malignancies characterized by ineffective production of healthy red blood cells, white blood cells and platelets, which can lead to anemia and frequent or severe infections, and can progress to Acute Myeloid Leukemia (AML). People with MDS who develop anemia often require regular blood transfusions to increase the number of healthy red blood cells in circulation. Frequent transfusions are associated with an increased risk of transfusion reactions, infections and iron overload. There are approximately 50,000 patients with MDS in the EU5 countries (France, Germany, Italy, Spain and the United Kingdom).
BELIEVE is a phase 3, randomized, double-blind, placebo-controlled multi-center study comparing Reblozyl plus BSC versus placebo plus BSC in adults who require regular RBC transfusions (6-20 RBC units per 24 weeks with no transfusion-free period greater than 35 days during that period) due to beta thalassemia.
The trial showed a statistically significant improvement in RBC transfusion burden during weeks 13 to 24 compared to the baseline 12-week interval prior to randomization (21.4% Reblozyl versus 4.5% placebo), meeting the study’s primary endpoint. The trial also met the secondary endpoint of transfusion burden reduction of at least 33% (with a reduction of at least two units) during weeks 37 to 48, which was achieved in a significantly greater proportion of patients receiving Reblozyl versus placebo. The trial also met an exploratory endpoint, with 70.5% of patients treated with Reblozyl achieving at least a 33% reduction in RBC transfusion burden of at least two units for any 12 consecutive weeks compared to the 12-week interval prior to treatment, compared to 29.5% of patients on placebo.
The majority of TEAEs were Grade 1-2. Discontinuation due to an adverse reaction (Grades 1-4) occurred in 5.4% of patients who received Reblozyl. The most common adverse reactions (>10%) were headache, bone pain, arthralgia, fatigue, cough, abdominal pain, diarrhea and dizziness.
Results of the BELIEVE trial were first presented at the ASH Annual Meeting in December 2018 and selected for the Best of ASH. The New England Journal of Medicine published the BELIEVE trial results in March 2020.
Beta thalassemia is an inherited blood disorder caused by a genetic defect in hemoglobin. The disease is associated with ineffective erythropoiesis, which results in the production of fewer and less healthy RBCs, often leading to severe anemia—a condition that can be debilitating and can lead to other complications for patients—as well as other serious health issues. Treatment options for anemia associated with beta thalassemia are limited, consisting mainly of frequent RBC transfusions that have the potential to contribute to iron overload, which can cause serious complications such as organ damage. Across the United States, Germany, France, Italy, Spain and the United Kingdom, there are approximately 17,000 patients with beta thalassemia.
Reblozyl (luspatercept-aamt), a first-in-class erythroid maturation agent, promotes late-stage red blood cell maturation in animal models. Bristol Myers Squibb and Acceleron are jointly developing Reblozyl as part of a global collaboration. Reblozyl is currently approved in the U.S. for the treatment of: anemia in adult patients with beta thalassemia who require regular red blood cell transfusions, and anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
Reblozyl is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia.